The long-term objective of this research project is to investigate perceptual, anatomical, and physiological consequences of sensorineural hearing loss (SNHL). The first specific aim will examine auditory deficits in C57BL/6J mice which serve as an animal model of presbycusis, the progressive loss of high-frequency hearing that afflicts most adult humans. When outer hair cells are lost in the progression of SNHL, the resulting disturbance of active cochlear mechanics is presumed to decrease auditory sensitivity and frequency tuning. This interpretation will be tested in detail by correlating behavioral measures of absolute threshold and frequency resolution at various stages of hearing loss with structural changes in the cochlea, auditory nerve, and cochlear nucleus. It is hypothesized that the onset of behaviorally-assessed perceptual deficits will be correlated with ultrastructural changes of the peripheral innervation before gross cochlear degeneration leads to significant hair cell loss. These findings may lead to a better understanding of the importance of early clinical interventions for the treatment of profound SNHL. Olivocochlear efferent fibers that project from the auditory brainstem to the cochlea terminate upon outer hair cells; for this reason, the most common patterns of SNHL disrupt both afferent and efferent processes in the auditory periphery. The second specific aim will isolate the discrete functional consequences of a compromised efferent feedback system by measuring the hearing thresholds of alpha-9 knockout mice in quiet and in continuo9us background noise. Recent physiological studies have shown that these mutant mice exhibit normal afferent responses but no obvious cochlear efferent activity because cholinergic olivocochlear projections cannot function in the absence of alpha-9 acetylchol9ne receptors. Based on the results of previous olivocochlear lesioning experiments in other species, it is hypothesized that genetically de-efferented mice will be more sensitive to noise masking effects than normal controls. These studies may explain why current hearing aid designs fail to function effectively in the presence of environmental noise.